Effect of Original Peptide Derivatives of Galantamine on Passive Avoidance in Mice.

The effect of original peptide derivatives of galantamine on scopolamine-induced memory impairment in mice was assessed using the passive avoidance test over 12 days. It was found that some galantamine derivatives administered in a dose of 1/20LD50 improved the memory in experimental mice, especially on days 5-12 of the experiment.

The optimizing action of the synthetic peptide Selank on a conditioned active avoidance reflex in rats.

The actions of the synthetic heptapeptide preparation Selank on learning and memory processes in rats with initially low levels of learning ability were compared with those in normal rats, using a method based on acquisition of a conditioned active avoidance reflex, with repeated administration of peptide 15 min before the start of training sessions for four days. The effects of Selank (300 microg/kg) were compared with the effects of the nootrope piracetam (400 mg/kg). These experiments showed that Selank significantly activated the learning process in rats with initially poor learning ability, with effects apparent after first dose on training day 1. The effect progressively increased on repeated administration of Selank: the total number of correct solutions increased and the number of errors decreased (p < 0.05). The maximum optimizing activity of Selank on learning in normal rats was seen on day 3 of repeated administration and training, i.e., after formation of the initial consolidation phase. The dynamic features of the development of the activating action of Selank and piracetam were described. Comparison of the results obtained here with data on the anti-anxiety actions of Selank suggested potential for its use in optimizing mnestic functions in conditions of elevated emotional tension.

[Optimizing action of synthetic peptide Selank on active avoidance conditioning test in rats]. / Optimiziruiushchee deistvie sinteticheskogo peptida Selanka na uslovnyi refleks aktivnogo izbeganiia u krys.

The action of a synthetic peptide Selank on learning and memory in active avoidance conditioning test was studied in rats with initially low learning ability and normal animals. The peptide was administered repeatedly 15 min prior the training session (4 days). The effect of Selank (300 micrograms/kg) was compared to that of Pyracetam (400 mg/kg). Selank was found to significantly improve learning in rats with low level ability even after a single administration on the first day of training session. The effect progressively increased with repeated Selank treatment: the total numbers of reactions and correct reactions increased, and the number of errors decreased (p < 0.05). In normal rats, the effect was maximal on the third day of treatment and training, i.e., after the completed initial consolidation. Some distinguishing features were revealed in the dynamics of activatory effects of Selank and Pyracetam. These data together with the evidence for ansiolytic effect of Selank show that this drug is promising for optimization of mnestic functions under conditions of high emotional stress.

New metal complexes of 4-methyl-7-hydroxycoumarin sodium salt and their pharmacological activity.

Complexes of copper (II), zinc (II), nickel (II), cobalt (II) and iron (III) with 4-methyl-7-hydroxycoumarin sodium salt (Mendiaxon, Hymecromone) were synthesized by mixing of equimolar amounts of the respective metal nitrates and 4-methyl-7-hydroxycoumarin sodium salt in water. The complexes were characterized and identified by elemental analysis, conductivities, IR, 1H NMR spectroscopy and mass spectral data. DTA and TGA have been applied to study the compositions of the compounds. Thermal analysis of the complexes indicate the formation of compounds which correspond to the compositions Met(HL)2 x nH2O, where Met = Cu, Zn, Ni, Co; n = 2, 3 or 4 and Fe(HL)3 x 5H2O. The newly synthesized compounds were assayed for acute intraperitoneal and per oral toxicity, influence on blood clotting time and the most active complex was investigated for spasmolytic activity.

Synthesis, toxicological, and pharmacological assessment of some oximes and aldehyde condensation products of 4-hydroxycoumarin.

The synthesis of condensation products of 4-hydroxycoumarin and nitro-substituted aromatic aldehydes as well as oximes of drugs with anticoagulant activity is described. The acute toxicity of the compounds was studied in mice by oral and intraperitoneal administration. A comparative pharmacological study of the in vivo anticoagulant effects of Warfarin derivatives showed that the new compounds have different anticoagulant activity. 4-Hydroxy-3-[1- (4-chlorophenyl)-3-oxobutyl]-2H-1-benzopyran-2-one, oxime 3 showed anticoagulant effect similar to Warfarin and Coumachlor, but its acute toxicity was higher than that of the reference drugs.

Synthesis, toxicological and pharmacological assessment of morpholinooximes.

The synthesis, pharmacology and toxicology of four morpholine derivatives from 1-(2-arylmorpholino)-3-phenyl-3-propanonoxime and the synthesis of two anilides are described. The structures of the synthesized derivatives were proved by IR, 1H NMR and occasionally with 13C NMR. The acute toxicity of the compounds in mice was determined. A comparative pharmacological study of the in vivo effect on the central nervous system was realised by the following screening tests: pentobarbital induced sleeping time, locomotor activity and behaviour despair test for antidepressive activity. The most active compound was 1-(2-phenylmorpholino)-3-phenyl-3-propanonoxime (2b) which showed low toxicity and antidepressive activity at a dose of 1/10 LD50.

[Interaction of piracetam with 3H-imipramine binding sites and the GAMA-benzodiazepine receptor complex of brain membranes]. / Vzaimodeistvie piratsetama s mestami spetsificheskogo sviazyvaniia 3H-imipramina i GAMK-benzodiazepinovym retseptornym kompleksom membran golovnogo mozga.

Piracetam at a concentration of 10(-6) M was shown to behave as a noncompetitive inhibitor of 3H-imipramine specific binding to rat brain membranes. At the same time piracetam failed to influence specific binding of 3H-mianserin to membranes of guinea-pig cerebellum, which is indicative of its inability to suppress histamine H1 receptors, a component of 3H-imipramine specific binding sites. At a concentration of 10(-4) M piracetam does not change specific binding of 3H-flunitrazepam to rat hippocampal membranes in the absence of GABA, but in the presence of 5 X 10(-5) M GABA, like atypical tranquilizer mebicar, acts as a competitor of 3H-flunitrasepam binding. Though Ro-15 1788 did not suppress anxyolytic piracetam (and mebicar) effect, our results give evidence of a possible involvement of GABA-benzodiazepine supramolecular complex in the anxiolytic activity of piracetam.

[Effect of chronic psychogenic stress on a number of behavioral and neurochemical characteristics of rats]. / Vliianie khronicheskogo psikhogennogo stressa na riad povedencheskikh i neirokhimicheskikh kharakteristik krys.

Fifteen-day chronic stress with randomized footshock reinforcement (group 4) causes profound steady disturbances in the animal behavior. With the use of regular aversive reinforcement in the shuttle-box the rats were divided into two groups: "escaping" (group 2) and "non-escaping" (group 3). Minor behavioral disturbances were observed in group 2, moderate in group 3 and maximum in group 4. In the latter group "down-regulation" of beta-adrenoceptors and benzodiazepine receptors was observed. The receptor changes appear to be rather the result of psychogenic factors caused by randomized reinforcement than of physical stress as such.

[Behavioral and radioreceptor analysis of viloxazine stereoisomers]. / Povedencheskii i radioprotektornyi analiz stereoizomerov viloksazina.

The differences in the pharmacological effects of R(+)- and S(-)-isomers of the atypical antidepressant viloxazin were discovered in two behavioral models. The S(-)-isomer appeared 5 times as active as the R(+)-isomer under acute administration. In chronic administration, (15 days), the R(+)-isomer appeared ineffective. Comparison of the affinity of the racemate, R(+) and S(-)-isomers for alpha 1-, alpha 2- and beta-adrenoreceptors, as well as for serotonin, C1, benzodiazepine, imipramine and dopamine receptors did not demonstrate any stereospecificity of viloxazin isomers. It is assumed that some other receptors (histamine, acetylcholine) present the targets for the pharmacological action of viloxazin or the latter one has, like zimelidin , specific binding sites of its own.

[Effect of chronic use of antidepressants on the state of benzodiazepine receptors in the mouse brain]. / Vliianie khronicheskogo primeneniia antidepressantov na sostoianie benzodiazepinovykh retseptorov golovnogo mozga myshi.

A study was made of the effect of a two-week administration of chlorimipramine, zimelidine and a morpholine derivative on benzodiazepine receptors of the mouse brain. The animals which received antidepressants demonstrated a significant increase in the binding sites of 3H-flunitrazepam without any changes in the dissociation constant as compared to control. The data on the evoked aggressiveness and latency of tonic corasole convulsions in the antidepressant-treated animals support the functional importance of the discovered changes in benzodiazepine receptors.